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Home Drugs Novel-saframycin-A-derivatives-and-process-for-producing-the-same

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 Novel saframycin A derivatives and process for producing the same

Details
Inventors: Arai, Tadashi; Mikami, Yuzuru;
Assignee: Arai; Tadashi (Tokyo, JP)
Primary Examiner: Wiseman; Thomas G.
Assistant Examiner: Patterson, Jr.; Charles L.
Attorney, Agent or Firm: Wenderoth, Lind & Ponack

Disclosed are compounds of the formula ##STR1## wherein R represents hydrogen or C.sub.1 -C.sub.4 -alkyl. These compounds are obtained by fermentation of the known saframycin A producing strain Streptomyces lavendulae No. 314 and by reaction with the amino acids L-tyrosine, L-methionine, glycine and HOOC-(CH)NH.sub.2 -CH.sub.2 -R. When R is hydrogen, saframycin Y.sub.3 and when R is methyl, saframycin Y.sub.d-1 are produced.

DETAILED DESCRIPTION What is claimed is: 1.
A process for the preparation of a compound of the formula ##STR4## wherein R represents hydrogen or C.
sub.
1 -C.
sub.
4 -alkyl comprising (a) suspending a biomass of a strain of streptomyces capable of producing saframycin A in an aqueous medium; (b) adding to said suspension glycine, L-tyrosine, L-methionine, and an amino acid of the formula HO.
sub.
2 CCH(NH.
sub.
2)--CH.
sub.
2 --R (II) wherein R is as defined above, either as individual amino acids or peptides consisting of amino acids selected from glycine, L-tyrosine, L-methionine, and the amino acid of formula II, or mixtures of said amino acids and said peptides to yield an enriched suspension; (c) incubating said enriched suspension; (d) filtering the result of step c; and (e) adding a cyanide salt to the filtrate obtained from step d to result in said compound of formula I.
2.
The process of claim 1 which further comprises isolating said compound of formula I from the result of step e.
3.
The process of claim 1 which further comprises converting said compound of formula I to an acid addition salt thereof.
4.
The process of claim 3 wherein said acid addition salt is pharmaceutically acceptable.
5.
The process of claim 1 wherein said biomass is obtained by inoculating a culture medium containing a carbon source, a nitrogen source, and essential trace elements with a strain of streptomyces capable of producing saframycin A; culturing said inoculated medium at a temperature of about 25.
degree.
C.
to about 35.
degree.
C.
, at a pH of about 4.
0 to about 7.
5, under aerobic conditions to yield a biomass in said culture; and isolating said biomass therefrom.
6.
A process for the preparation of a compound of the formula ##STR5## wherein R represents hydrogen comprising (a) suspending a biomass of a strain of streptomyces capable of producing saframycin A in an aqueous medium; (b) adding to said suspension glycine, L-tyrosine, and L-methionine, either as individual amino acids or as peptides consisting of glycine, L-tyrosine, and L-methionine, or mixtures of said amino acids and said peptides to yield an enriched suspension; (c) incubating said enriched suspension; (d) filtering the result of step c; (e) adding a cyanide salt to the filtrate obtained from step d to result in said compound of formula I; and (f) then isolating the compound of formula I



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